The breakdown of proteins and endogenous peptides in the brain by cerebral proteinases and peptidases will be studied. The rate of breakdown of purified brain proteins such as histones, proteolipids, S- 100, neurostenin, neurotubulin, and neurophysin by acid and neutral proteinase will be compared. Basic protein of myelin and its peptide products will be studied in detail with a highly purified enzyme fraction to determine the peptide bond specificity of brain proteinase. The encephalitogenicity of peptide fragments of basic protein will be tested and the effect of inhibition of acid proteinase in vivo on the development of experimental allergic encephalitis will be measured. Peptide breakdown will be measured with natural or peptide hormones of the hypothalamus and pituitary and with some synthetic analogs. Emphasis will be on measuring the metabolic products and the properties (especially bond specificity) of the specific enzymes involved in peptide hormone metabolism. It will be established whether peptide hormones can be enzymatically released or activated and how their level is affected when peptidases or proteases are inhibited. Primarily the following compounds will be tested: oxytocin, vasopressin, bradykinin, angiotensin I and II, and some hypothalamic releasing and inhibitor factors (MSHRF, TRH, LRF).